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5309165 
Journal Article 
Synthesis of lamivudine stearate and antiviral activity of stearic acid-g-chitosan oligosaccharide polymeric micelles delivery system 
Li, Q; Du, YZ; Yuan, H; Zhang, XG; Miao, J; Cui, FD; Hu, FQ 
2010 
Yes 
European Journal of Pharmaceutical Sciences
ISSN: 0928-0987
EISSN: 1879-0720 
41 
3-4 
498-507 
English 
20728535 
WOS:000283690000010 
To increase lipophilicity of water-soluble antiviral drug, the prodrug of Lamivudine (LA), Lamivudine stearate (LAS) was synthesized via ester linkage between LA and stearic acid. After the esterification, the octanol-water partition coefficient (logP) of LA increased from -0.95 to 1.82. Stearic acid-g-chitosan oligosaccharide (CSO-SA) micelles have demonstrated fast internalization and accumulation ability to tumor cells. Herein, the CSO-SA with 3.79% amino substitution degree (SD) was prepared for loading LAS. The critical micelle concentration (CMC) of CSO-SA was about 0.032mg/ml. The micelles with 1mg/ml CSO-SA concentration had 460.8nm average diameters with a narrow size distribution and 29.7mV surface zeta potential. After LAS was incorporated, the micellar size decreased and the zeta potential increased. The LAS loaded CSO-SA micelles (CSO-SA/LAS) possessed high entrapment efficiency and drug loading. LA release from CSO-SA/LAS showed a pH-dependent behavior. The release rate of LA from CSO-SA/LAS increased significantly as the pH of release medium reduced from 7.4 to 6.2. CSO-SA/LAS presented a low cytotoxicity and high cellular uptake percentage of LAS against HBV transfected tumor cells (HepG2.2.15). In vitro anti-HBV activities of CSO-SA/LAS presented more conspicuous inhibitory effects on antigen expression and DNA replication compared with LA and LAS.